Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 5, Issue 12, Pages 1304-1307Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ml5003635
Keywords
Ebselen; mitochondria; H2O2; radiation; mitigators apoptosis
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Funding
- NIH Grant [U19AI068021, HL114453, NS061817]
- Human Frontier Science Program [RGP0013]
- MRC [MC_U105663142] Funding Source: UKRI
- Medical Research Council [MC_U105663142] Funding Source: researchfish
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Ionizing radiation (IR) triggers mitochondrial overproduction of H2O2 and accumulation of lipid hydroperoxides leading to the induction of apoptotic and necroptotic cell death pathways. Given the high catalytic efficiency of the seleno-enzyme glutathione peroxidase (Gpx) toward reduction of lipid hydroperoxides and H2O2, we tested the potential of mitochondria-targeted derivatives of ebselen to mitigate the deleterious effects of IR. We report that 2-[[2-[4-(3-oxo-1,2-benzoselenazol-2-yl)phenyl]acetyl]amino]ethyl-triphenyl-phosphonium chloride (MitoPeroxidase 2) was effective in reducing lipid hydroperoxides, preventing apoptotic cell death, and, when administered 24 h postirradiation, increased the survival of mice exposed to whole body gamma-irradiation.
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